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Sarah Franklin is professor of sociology and director of the Reproductive Sociology Research Group at the University of Cambridge, UK, and author of Dolly Mixtures.
By cloning Dolly the sheep in 1996, embryologist Ian Wilmut rewrote the biological rule book as well as the playbook for science governance. Wilmut was a top-tier scientist whose self-effacing manner helped him to champion the biosciences for a global audience. But he had plenty of help in his endeavours, not least from Dolly herself — one of the world’s most iconic scientific progeny. Wilmut has died, aged 79.
Wilmut’s discovery that viable mammalian offspring could be produced using the nucleus of a differentiated cell blew a huge hole in the idea that genetic instructions were lost when cells committed themselves to specialized pathways. A new theory arose of noisy genetic chit-chat between nuclear DNA and the wider cellular ecosystem. For translational biological and biomedical sciences, the implications were vast. After Dolly, regenerative medicine — the growth of replacement cells and tissues — gained traction as one of the most promising fields of therapeutic development.
Born in a village in Warwickshire, UK, Wilmut showed an interest in biology at school and chose to study agriculture at the University of Nottingham, UK, after working on farms as a teenager. He trained in embryology at the Animal Research Station of the University of Cambridge, UK. There his supervisor, Chris Polge, had developed methods of freezing and thawing semen from livestock. Wilmut performed the first successful transfer of a previously frozen embryo into a surrogate heifer, which gave birth in 1973 to Frostie, a healthy bull calf.
Wilmut moved to the Roslin Institute at the University of Edinburgh, UK, in 1973. The experiments that he performed there were daunting and complex. He combined scientific and technical knowledge with clinical and veterinary expertise in an effort that ultimately led to Dolly’s development. Wilmut’s early work on nuclear-transfer techniques led him to consider more efficient ways of producing transgenic animals. A series of cloned lambs followed, including Megan and Morag (from cultured embryonic cells in 1995), and Taffy and Tweed (from cultured fetal cells in 1996).
Cloning a cultured adult cell required an understanding of the role of the cell cycle in the programming of cells. To work, the nucleus had to be transferred from a cell that was in a dormant or ‘quiescent’ state, when it was not dividing. Starting in the mid-1990s, Wilmut and his collaborator Keith Campbell began transferring the nuclei of cultured adult cells that were in this quiescent phase into egg cells that had had their nuclei removed. Dolly was the result of this method — such a feat had previously been considered biologically impossible.
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